Process for preparing 1, 2, 4-triazoles



Christoph J. Gruudrnnnh and Rudi F. W. Riitz, Columbus,

Ohio, assignors to Olin Mathieson Chemical Corporation, a corporation ofVirginia No Drawing. Application March 29, 1956, Serial No. 574,586

5 Claims. (Cl. 260-308) Our invention relates to a novel method ofpreparing 1,2,4-triazoles. More particularly, our invention relates tothe preparation of 1,2,4-triazoles from 1,3,5-triazine and a hydrazinehydrohalide.

It is known that 1,3,5-triazine reacts with ammonium chloride to formformamidine hydrochloride. Furthermore, co-pending application, SerialNo. 467,229, filed November 5, 1954, of Christoph J. Grundmann andAlfred Kreutzberger, teaches that 1,3,5-triazine reacts with primaryamines to form disubstituted formamidines. In view of the formation ofamidines in the two former instances it was expected that 1,3,5-triazinewould react with hydrazine m-onohydrochloride to give the formamidrazonehydrochloride: HzNCH=NNHaHCL Surprisingly, however, we have discoveredthat the reaction of 1,3,5-triazine with a hydrazine hydrohalide resultsin the formation of a triazole ring. Thus, the following reactionoccurs:

c HCN a N N -Hx a n-r-aumx Hi dH wherein X is a halogen and R ishydrogen or an alkyl or aryl group.

The reaction is carried out by admixing the reactants. For example,1,3,5-triazine is melted with the hydrazine hydrohalide or the reactionis carried out in the presence of a suitable solvent. Particularlysuitable solvents are those in which the by-product ammonium halide isinsoluble. The solvent should be anhydrous and preferably one in whichthe triazole is sufficiently soluble to enable an easy separation of thereaction product. Examples of suitable solvents are organic liquids suchas lower aliphatic alcohols, e. g., methanol and ethanol. In some casesreaction occurs on mixing. It is desirable to reflux the reactionmixture, however. The reaction then can be carried out from roomtemperature to about 100 C. The ammonium halide is removed, for example,by filtration and the triazole is recovered, for example, bydistillation or crystallization.

Preferably, the reactants are used in stoichiometric proportions as thisresults in substantially quantitative yield of the triazoles.

The hydrazines useful in our invention include hydrazine andmonosubstituted hydrazines. The monosubstituted hydrazines useful in ourinvention include alkyl and aryl substituted hydrazines. Particularlyuseful alkylhydrazines are the lower alkylhydrazines in which the numberof carbon atoms in the alkyl group is less than 4, e. g.,methylhydrazine, ethylhydrazine and propylhydrazine. Usefularylhydrazines include phenylhydrazine, tolylhydrazine andalphanaphthylhydrazine. The aryl groups also can have substituents suchas halogens or nitro groups, e. g., p-nitrophenylhydrazine andp-bromophenylhydrazine are useful. The use of monosubstituted hydrazinesproduces l-substituted-l,2,4,-triazoles.

2,800,486 Patented July 23, 1957 ICC The hydrazines must be used in theform of their monohydrohalide salts. The hydrohalide is preferably thehydrochloride but other hydrohalide salts are useful, e. g., thehydrobromide, hydrofluoride and hydroiod dc- It is preferable to usesalts which dissolve in solvents suitable for the reaction, for examplemethanol or ethanol, or which have a sufficiently low melting point inorder to furnish a homogenous melt with the l,3,5-triazine.

The 1,2,4-triazoles produced by the process of our invention are useful,for example, as intermediates in the preparation of many useful chemicalcompositions.

The process of our invention will be further illustrated by reference tothe following examples.

Example I About 600 milliliters of absolute ethanol was distilled overmetallic sodium and 16.2 grams of 1,3,5-triazine was dissolved therein.To this was added 20.55 grams of well powdered hydrazinemonohydrochloride and the mixture was refluxed for 8 hours. The mixturewas then cooled and 9 grams of ammonium chloride were filtered off. Uponthe addition of ether, an additional 7 grams of ammonium chlorideprecipitated. The red colored alcohol ether filtrate was evaporated invacuo to dryness, whereupon 21 grams of crystalline triazole remained.By recrystallizing the product from chloroform 20 grams of pure1,2,4-triazo1e was obtained. The purified product melted at 112 C. andwas obtained in 96 percent yield.

N Calculated for C2H3N3 60.87 28.63 Fund "l60.70 Example II A mixture of16.2 grams of 1,3,5-triazine and 43.4 grams of phenylhydrazinemonohydrochloride were refluxed in 200 milliliters of absolute ethanolfor 12 hours. After cooling, 12.5 grams of ammonium chloride werefiltered off and the filtrate was distilled to remove the alcohol. Thereremained 40 grams of a light colored oil which crystallized on chillingto 0 C. to almost pure 1- phenyl-l,2,4-triazole. The compound wasdistilled at atmospheric pressure and there was obtained 36 grams or 83percent of the theory of l-phenyl-l,2,4-triazole, which melted at 47 C.and boiled at 268 to 270 C.

N Calculated for Carma 28.95 28.63 mm "{2868 Example III A solutioncomprising 3.24 grams of 1,3,5-triazine in 30 milliliters of absoluteethanol was made up. To this solution was added 4.95 grams ofmethylhydrazine monohy-drochloride and the reaction started immediatelywith the evolution of heat. It was then completed by refluxing for 8hours. The product was then filtered to remove 2.2 grams of ammoniumchloride and the alcohol was removed by distillation. Upon extractingthe oily residue with ether an additional 0.9 gram of ammonium chlorideprecipitated and was removed by filtration. The etherial filtrate wasthen distilled to leave behind 5 grams of yellowish oil which was almostpure 1-methyl-l,2,4-triazole. Upon distillation of the latter atatmospheric pressure there was obtained 4.0 grams or 81 percent of thetheory of l methyl-l,2,4-triazole which melted at 20 C. and boiled at to176 C.

N Calculated for CzHsNa 50.57 50.12 Found "l 50.10

3 We claim: 1. A process for preparing 1,2,4-triazoles which comprisesadmixing l,3,5-triazine with a hydrazine hydrohalide of the formula:

wherein R is selected from the group consisting of hydrogen and loweralkyl, aryl, haloaryl, an nitroaryl radicals, said aryl radicals beinghydrocarbon radicals of not more than 10 carbon atoms, and X is ahalogen.

2. The process of claim 1 in which the hydrazine is hydrazinemonohydrochloride.

3. The process of claim 1 in which the hydrazine is methylhydrazinemonohydrochloride.

4. The process of claim 1 in which the hydrazine is phenylhydrazinemonohydrochloride.

5. The process of claim 1 in which the process is carried out at atemperature of about room temperature to about 100" C.

No references cited.

1. A PROCESS OF PREPARING 1,2,4-TRIAZOLES WHICH COMPRISES ADMIXING1,3,5-TRIAZINE HYDROHALIDE OF THE FORMULA: